A COMBINATION OF INSULIN-LIKE GROWTH-FACTOR-I AND PLATELET-DERIVED GROWTH-FACTOR ENHANCES MYELINATION BUT DIMINISHES AXONAL REGENERATION INTO SCHWANN-CELL GRAFTS IN THE ADULT-RAT SPINAL-CORD

Insulin-like growth factor-I (IGF-I) promotes axonal regeneration in t he peripheral nervous system and this effect is enhanced by platelet-d erived growth factor (PDGF). We decided, therefore, to study the effec ts of these factors on axonal regeneration in the adult rat spinal cor d. Semipermeable polymer tubes, closed at the distal end, containing M atrigel mixed with cultured rat Schwann cells and IGF-I/PDGF, were pla ced at the proximal stump of the spinal cord after removal of the thor acic T9-11 segments. Control animals received implants of only Matrige l and Schwann cells or only Matrigel and IGF-I/PDGF, Four weeks after implantation, electron microscopic analysis showed that the addition o f IGF-I/PDGF resulted in an increase in the myelinated:unmyelinated fi ber ratio from 1:7 to 1:3 at 3 mm in the Schwann cell graft, and that myelin sheath thickness was increased 2-fold. The reduced number of un myelinated axons was striking in electron micrographs. These results s uggested that IGF-I/PDGF enhanced myelin formation of regenerated axon s in Schwann cell implants, but there was a 36% decrease in the total number of myelinated axons at the 3 mm level of the graft. This findin g and the altered myelinated:unmyelinated fiber ratio revealed that th e overall fiber regeneration into Schwann cell implants was diminished up to 63% by IGF-I/PDGF. Histological evaluation revealed that there were more larger cavities in tissue at the proximal spinal cord-graft interface in animals receiving a Schwann cell implant with IGF-I/PDGF. Such cavitation might have contributed to the reduction in axonal ing rowth. In sum, the results indicate that whereas the combination of IG F-I and PDGF enhances myelination of regenerating spinal cord axons en tering implants of Matrigel and Schwann cells after midthoracic transe ction, the overall regeneration of axons into such Schwann cell grafts is diminished. (C) 1997 Wiley-Liss, Inc.